Utility of pre- and post-pembrolizumab (Pembro) Vesical Imaging–Reporting and Data System (VIRADS) to predict the pathological response in muscle-invasive urothelial bladder cancer (MIBC): An analysis of the PURE-01 cohort.
Authors: Giorgio Brembilla, Giuseppe Basile, Marco Bandini, Daniele Raggi, Laura Marandino, Tiago Costa de Padua, Damiano Alfio Patanè, Emanuele Crupi, Andrea Del Prete, Renzo Colombo, Maurizio Colecchia, Roberta Lucianò, Marco Moschini, Jeffrey S. Ross, Alberto Briganti, Francesco Montorsi, Francesco De Cobelli, Andrea Necchi
Journal: Journal of Clinical Oncology (2023)

552 Background: The possibility to predict the pathologic complete response (pT0) or downstaging (pT≤1) after neoadjuvant therapy may have profound impact on the management of MIBC and orient next-generation bladder-sparing trials. The VIRADS is a standardized reporting system that uses mpMRI parameters to predict the probability of MIBC. No studies have analyzed the ability of VIRADS to predict the pT0 or pT≤1 response post-immunotherapy (IO). Methods: In PURE-01 patients (pts) were staged with bladder multiparametric magnetic resonance imaging (mpMRI: T2-weighted imaging, diffusion-weighted imaging, dynamic contrast enhancement) before and after treatment (3 cycles of pembro) prior to radical cystectomy (RC). All mpMRI scans were centrally reviewed. Logistic regression models analyzed pre- and post-pembro VIRADS against pT≤1 (primary endpoint) and pT0 (secondary endpoint). VIRADS scores were dichotomized between 0-3 and 4-5. Covariates included cT-stage, age, gender, PD-L1 combined positive score (CPS) and tumor mutational burden (TMB). Results: In total, 58 pts were had centrally-reviewed MRI scans (N=116 mpMRI), treated between 02/17 and 08/18. Demographic characteristics and outcomes were generally similar between the all-treated and VIRADS-evaluable populations of PURE-01. Median age was 65 years, 52 (89%) had pure/predominant urothelial carcinoma (UC) histology, 25 (43.1%) had cT3-4N0 MIBC. Pre-pembro: 8 pts (13.8%) had no measurable disease (VIRADS=0), 20 (34.5%) a VIRADS 1-3 score, and 30 (51.7%) had a VIRADS 4-5 score. Six pts (10.3%) had a downstage from VIRADS 4-5 to VIRADS 0-3 post-pembro. Both pre-pembro and post-pembro VIRADS 0-3 scores were significantly associated with pT≤1 endpoint on multivariable analyses (MVA): the strongest effect was seen with post-pembro VIRADS 0-3 against pT≤1 response (OR: 30.2, 95%CI: 6.2-223.2, p&lt;0.0001). The AUC of this model was 0.92. Regarding pre-pembro VIRADS 0-3: OR: 4.35, 95%CI: 1.1-19.7, p=0.04; AUC: 0.83. CPS was another significant variable for pT≤1 endpoint only in MVA using pre-pembro VIRADS 0-3 (OR: 1.02, 95%CI: 1-1.05, p=0.02). Post-pembro VIRADS 0-3 was also associated with pT0 on MVA (OR: 4.59, 95%CI: 1.2-19.6, p=0.02; AUC: 0.78), whereas pre-pembro VIRADS was not (p=0.13). Mean apparent diffusion coefficients (ADC) were similar between pre- and post-pembro lesions (0.86 vs 0.87). Conclusions: To our knowledge, this is the first evidence establishing the predictivity of the VIRADS score towards the pathological downstaging, both in the pre and post IO settings. Post-pembro VIRADS, along with the combination of pre-pembro VIRADS and CPS, emerged as the strongest features based on which selecting pts for bladder-sparing strategies. Clinical trial information: NCT02736266 .